CORE C: The objectives of the core are to facilitate the discovery and development of inhibitors of virulence factor proteins from biowarfare pathogens that are targeted by the projects. The Core will provide a small molecule high throughput screening (HTS) facility for screening proteins. These inhibitors will be verified and transferred for NMR-based optimization strategies to enhance their selectivity and affinity amongst other properties. Core chemists, in collaboration, will develop designs for focused analog libraries based on NMR data. The specific aims are: Aim 1. Provide small molecule high throughput (HTS) screening of virulence factors. These factors include CrmA and Spi1, a detoxified mutant of BoNT/C, Yop J, YopH, and new virulence factors. Aim 2. Provide a chemical synthesis lab and synthetic assistance for the NMR-based optimization of small molecules and for resynthesis of lead compounds.